Ischemic heart disease is the most common cause of morbidity and mortality in the population over the age of sixty-five. Sullivan, L. W. 1990. Healthy people 2000. N Engl J Med. 323:1065-1067; Wei, J. Y. 1992. Age and the cardiovascular system. N Engl J Med. 327:1735-1739; Association, A. H. 1993-1995. Heart and stroke facts statistical supplement/1994-1996. Dallas, Tex.: The Association. Elucidation of the cellular and molecular pathways that are impaired with aging is critical to develop specific strategies to prevent and reduce the pathology of cardiovascular disease associated with advancing age.
In younger individuals, myocardial ischemia induces the development of a collateral vasculature supply that partially protects the cardiac tissue from subsequent coronary events. Hirai et al. (1989) Circulation. 79:791-796; Ejiri et al. (1990) J Cardiol. 20:31-37; Kodama et al. (1996). J Am Coll Cardiol. 27:1133-1139; Banerjee et al., (1993) Int J Cardiol. 38:263-271. However, angiogenesis is impaired in older heart and peripheral vascular beds. Hudlicka et al. (1996) J Vasc Res. 33:266-287; Isoyama (1994) Drugs Aging. 5:102-115; Tomanek et al. (1990) Am J Physiol. 259:H1681-1687; Anversa et al. (1994) Am J Physiol. 267:H1062-1073; Azhar et al. (1999) Exp Gerontol. 34:699-714; Rakusan et al. (1994) Cardiovasc Res. 28:969-972; Rivard et al. (1999) Circulation. 99:111-120; Reed et al. (2000) J Cell Biochem. 77:116-126. The etiology of the impaired angiogenic activity in the senescent heart is not known. In fact, despite recent advances in our understanding of the molecular pathways regulating angiogenesis during embryonic development, the mechanistic alterations in angiogenic function in the senescent vasculature are not well understood. Therefore, new approaches are needed for counteracting the age-associated changes in angiogenic pathways within the cardiac endothelium.